The impact of response on bone-directed therapy in patients with multiple myeloma

Significant benefits for zoledronic acid (ZOL) over clodronate acid (CLO) were seen in the Medical Research Council Myeloma IX randomized trial. ZOL significantly reduced skeletalrelated events (SREs), and improved progression-free survival and overall survival (OS), making it the bisphosphonate of choice for newly diagnosed myeloma patients. In this analysis of Myeloma IX data, we have investigated the impact of response on bone disease in 1111 transplant-eligible patients. At posttransplant day 100, complete response (CR) was seen in 48% of patients, very good partial response (VGPR) in 20%, and partial response (PR) in 23%. For patients in VGPR or less, ZOL was superior to CLO in reducing SREs (P 5.048), whereas for patients in CR, both agents were equivalent (P 5.83). For OS, ZOL was associated with a significant benefit in patients in PR (P 5.0091). No difference in OS was seen with patients in CR (P 5.91) or VGPR (P 5.74). These findings indicate that response category posttransplant may influence the impact of bisphosphonate therapy. This trial was registered as #ISRCTN68454111 at www.isrctn.org.